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The Projected Impact of Population-Wide Achievement of LDL Cholesterol <70 mg/dL on the Number of Recurrent Events Among US Adults with ASCVD

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Abstract

Purpose

Adults with atherosclerotic cardiovascular disease (ASCVD) are recommended high-intensity statins, with those at very high risk for recurrent events recommended adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor if their low-density lipoprotein cholesterol (LDL-C) is ≥70 mg/dL. We estimated the number of recurrent ASCVD events potentially averted if all adults in the United States (US) ≥45 years of age with ASCVD achieved an LDL-C <70 mg/dL.

Methods

The number of US adults with ASCVD and LDL-C ≥70 mg/dL was estimated from the National Health and Nutrition Examination Survey 2009–2016 (n = 596). The 10-year cumulative incidence of recurrent ASCVD events was estimated from the REasons for Geographic And Racial Differences in Stroke study (n = 5390), weighted to the US population by age, race, and sex. The ASCVD risk reduction by achieving an LDL-C <70 mg/dL was estimated from meta-analyses of lipid-lowering treatment trials.

Results

Overall, 14.7 (95% CI, 13.7–15.8) million US adults had ASCVD, of whom 11.6 (95% CI, 10.6–12.5) million had LDL-C ≥70 mg/dL. The 10-year cumulative incidence of ASCVD events was 24.3% (95% CI, 23.2–25.6%). We projected that 2.823 (95% CI, 2.543–3.091) million ASCVD events would occur over 10 years among US adults with ASCVD and LDL-C ≥70 mg/dL. Overall, 0.634 (95% CI, 0.542–0.737) million ASCVD events could potentially be averted if all US adults with ASCVD achieved and maintained LDL-C <70 mg/dL.

Conclusion

A substantial number of recurrent ASCVD events could be averted over 10 years if all US adults with ASCVD achieved, and maintained, an LDL-C <70 mg/dL.

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Acknowledgements

The design and conduct of the study, interpretation of the results, and preparation of the manuscript were supported through a research grant from Amgen, Inc. (Thousand Oaks, CA). The academic authors conducted all analyses and maintained the rights to publish this article. The REGARDS study is supported by a cooperative agreement U01 NS041588 co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging, National Institutes of Health, Department of Health and Human Service. Representatives of the funding agency have been involved in the review of the manuscript but not directly involved in the collection, management, analysis, or interpretation of the data. Additional support was provided by grants R01 HL080477 and K24 HL111154 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. The authors thank the other investigators, the staff, and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions and further information about the study can be found at http://www.regardsstudy.org.

Availability of Data Materials

The datasets generated and/or analyzed during the current study will be made available from the corresponding author upon reasonable request.

Declarations

Ethics Approval and Consent to Participate

The institutional review board at the University of Alabama at Birmingham approved the study and waived the requirement to obtain informed consent.

Consent for Publication

Not applicable.

Competing Interests

ECM receives research support from Amgen, Inc. VAB receives research support from Amgen, Inc.; serves on the executive steering committee of the ODYSSEY OUTCOMES trial (Sanofi); as National Coordinator for STRENGTH (Astra Zeneca), DalGene (Dalcor), and CLEAR (Esperion); and as local site investigator for ORION IV (Novartis). She served as a consultant to Sanofi in 2018 and is currently consulting for Pfizer. TMB receives research support from Amgen, Inc. and served as the local site investigator for STRENGTH (Astra Zeneca). EAJ receives research support from Amgen, Inc. and NIH; consulting fees from the American College of Cardiology and McKesson; expert witness for DeBlase Brown Everly, LLP; royalties from UpToDate, Inc.; and editor for the American Heart Association. MEF receives research support from Amgen, Inc., Novo Nordisk, and Novartis. EBL receives research support from Amgen, Inc. and consulting fees from Novartis. RSR receives research support from Amgen, Inc., Astra Zeneca, Novartis, and Regeneron; consulting fees from Amgen, Inc., Amryt, C5, CVS Caremark, Novartis, Regeneron, and 89 Bio; honoraria from Amgen, Inc., Kowa, and Regeneron; and royalties from Wolters Kluwer (UpToDate, Inc.) and has stock in MediMergent, LLC. MMS receives research support from Amgen, Inc. MW serves as a consultant for Amgen, Inc., Freeline, and Kyowa Kirin. JE, KKO, and SRR are employees of and have stock in Amgen, Inc. PM receives research support and consulting fees from Amgen, Inc. LDC receives research support from Amgen, Inc. No other disclosures were reported.

Funding

This work was funded by Amgen Inc., Thousand Oaks, CA.

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Authors and Affiliations

  1. Department of Epidemiology, University of Alabama at Birmingham, 1665 University Blvd, RPHB 523B, Birmingham, AL, 35233-0013, USA

    Emily C. McKinley, Ligong Chen, Lei Huang, Emily B. Levitan, Paul Muntner & Lisandro D. Colantonio

  2. Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Vera A. Bittner, Todd M. Brown & Elizabeth A. Jackson

  3. Amgen Inc., Thousand Oaks, CA, USA

    Jason Exter

  4. Peter Munk Cardiac Centre, University of Toronto and Heart and Stroke Richard Lewar Centre of Excellence, Toronto, ON, Canada

    Michael E. Farkouh

  5. Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA

    Kate K. Orroth & Stephanie R. Reading

  6. Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Robert S. Rosenson

  7. Department of Medicine, Weill Cornell Medicine, New York, NY, USA

    Monika M. Safford

  8. The George Institute for Global Health, University of New South Wales, Sydney, Australia

    Mark Woodward

  9. The George Institute for Global Health, School of Public Health, Imperial College London, London, UK

    Mark Woodward

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  1. Emily C. McKinley
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  2. Vera A. Bittner
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  15. Paul Muntner
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  16. Lisandro D. Colantonio
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Contributions

ECM, VAB, TMB, EAJ, MEF, EBL, RSR, MMS, JE, KKO, SRR, PM, and LDC contributed to the study concept, study design, interpretation of results, and manuscript content. LC and LH conducted the data analysis. The first draft of the manuscript was written by ECM. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Emily C. McKinley.

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McKinley, E.C., Bittner, V.A., Brown, T.M. et al. The Projected Impact of Population-Wide Achievement of LDL Cholesterol <70 mg/dL on the Number of Recurrent Events Among US Adults with ASCVD. Cardiovasc Drugs Ther 37, 107–116 (2023). https://doi.org/10.1007/s10557-021-07268-x

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